Colitis-induced alterations in response properties of visceral nociceptive neurons in the rat caudal medulla oblongata and their modulation by 5-HT3 receptor blockade.

Autor: Lyubashina OA; Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Nab. Makarova, Saint Petersburg 199034, Russia. Electronic address: olga@kolt.infran.ru., Sivachenko IB; Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Nab. Makarova, Saint Petersburg 199034, Russia. Electronic address: AVANS_d@mail.ru., Busygina II; Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Nab. Makarova, Saint Petersburg 199034, Russia. Electronic address: irina@kolt.infran.ru., Panteleev SS; Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Nab. Makarova, Saint Petersburg 199034, Russia. Electronic address: panteleev@kolt.infran.ru.
Jazyk: angličtina
Zdroj: Brain research bulletin [Brain Res Bull] 2018 Sep; Vol. 142, pp. 183-196. Date of Electronic Publication: 2018 Jul 19.
DOI: 10.1016/j.brainresbull.2018.07.013
Abstrakt: There is considerable clinical and experimental evidence that intestinal inflammation is associated with altered visceral nociceptive processing in the spinal cord and brain, but the underlying neuronal mechanisms, especially acting at the supraspinal level, remain unclear. Considering that the caudal ventrolateral medulla (CVLM) and the nucleus tractus solitarius (NTS) are the first sites for supraspinal processing of visceral pain signals, in the present study we evaluated the experimental colitis-induced changes in response properties of CVLM and NTS medullary neurons to noxious colorectal distension (CRD) in urethane-anesthetized adult male Wistar rats. To determine if gut inflammation alters the 5-HT 3 receptor-dependent modulation of visceral pain-related CVLM and NTS cells, we examined the effects of intravenously administered selective 5-HT 3 antagonist granisetron on ongoing and CRD-evoked activity of CVLM and NTS neurons in healthy control and colitic animals. In the absence of colonic pathology, the CVLM neurons were more excited by noxious CRD that the NTS cells, which demonstrated a greater tendency to be inhibited by the stimulation. The difference was eliminated after the development of colitis due to the increase in the proportion of CRD-excited neurons in both medullary regions associated with enhanced magnitude of the neuronal nociceptive responses. Intravenous granisetron (1 or 2 mg/kg) produced the dose-dependent suppression of the ongoing and evoked firing of CRD-excited cells within both the CVLM and NTS in normal conditions as well as was able to substantially reduce excitability of the caudal medullary neurons in the presence of colonic inflammation, arguing for the potential efficacy of the 5-HT 3 receptor blockade with granisetron against both acute and inflammatory abdominal pain. Taken together, the data obtained can contribute to a deeper understanding of supraspinal serotonergic mechanisms responsible for the persistence of visceral hypersensitivity and hyperalgesia triggered by colonic inflammation.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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